ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Grtp1 Safeguards Against Paternal Reproductive Aging and Intergenerational Behavioral Deficits by Preserving Redox Homeostasis.
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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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24 authors.
Yingdong Liu *Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Shanyao Liu *Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Haixin Liang *Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiani YangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yanhe LiShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiqing YinShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Xueguang ZhangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yan ZhangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Dandan BaiShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Zihui YanShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Zhuoao ZhangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yanping JiaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Kuisheng LiuShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yifan ShengShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiani XiangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Chenxiang XiShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Baoxing DongShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Xinyi LeiShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiayu ChenShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0003-4755-8901
Hong WangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yi GuoShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yanping ZhangShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Shaorong GaoShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0003-1041-3928
Wenqiang LiuShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0002-5974-9900
Funding
China Postdoctoral Science Foundation 2026M792972Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China JYB2025XDXM508Fundamental Research Funds for the Central Universities 22120250374Ministry of Science and Technology of ChinaNational Natural Science Foundation of China 32170589National Natural Science Foundation of China 32270909National Natural Science Foundation of China 32330030National Natural Science Foundation of China 32470907National Natural Science Foundation of China 32488101National Natural Science Foundation of China 324B2021National Natural Science Foundation of China 32570948National Natural Science Foundation of China 32570957Peak Disciplines (Type IV) of Institutions of Higher Learning in ShanghaiScience and Technology Commission of Shanghai Municipality 21JC1405500Shanghai Pilot Program for Basic ResearchShenzhen Medical Research Fund B2402013
Abstract
Oxidative stress is a primary mediator of male reproductive decline and offspring behavioral abnormalities. Unlike females, males exhibit enhanced antioxidant capacity and sustained fertility, but the mechanism is unclear. Here, using single-cell transcriptomics and cross-sex comparisons, we identify Grtp1 as critical for counteracting male reproductive aging and protecting offspring from behavioral deficits by preserving germline redox homeostasis and sperm DNA methylation stability. Grtp1 ablation recapitulates aging phenotypes, including oxidative stress, mitochondrial dysfunction, impaired spermatogenesis, and offspring anxiety and social deficits. Mechanistically, GRTP1 interacts with PRDX1/4 and TXN to maintain germline redox balance. Notably, growth hormone treatment in aged males rescues germline redox homeostasis, restores abnormal sperm DNA methylation and quality, and ameliorates offspring behavioral deficits in a Grtp1-dependent manner. Our study establishes GRTP1 as a key redox safeguard against male germline aging and highlights the GH-GRTP1 axis as a promising therapeutic target for age-related reproductive and intergenerational behavioral deficit.
Indexed as
behavioral abnormalitiesDNA methylationgrowth hormoneGrtp1male reproductive agingredox homeostasis
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